Hepatitis B virus clinical and virologic characteristics in an HIV perinatal transmission study in sub-Saharan Africa.

OBJECTIVES: To describe the clinical and virologic characteristics of HIV-HBV coinfection, including the predictors of high maternal HBV viral load in pregnant women with HIV in sub-Saharan Africa (SSA). METHODS: HPTN 046 was a HIV perinatal transmission clinical trial evaluating infant nevirapine vs. placebo. Women-infant pairs ( n  = 2016) were enrolled in SSA from 2007 to 2010; 1579 (78%) received antiretrovirals (ARV). Maternal delivery samples were retrospectively tested for hepatitis B surface antigen (HBsAg), and if positive, were tested for hepatitis B e antigen (HBeAg) and HBV viral load (VL). High HBV VL was defined as ≥10 6  IU/ml. RESULTS: Overall, 4.4% (88/2016) had HBV co-infection, with geographic variability ranging from 2.4% to 8.7% ( P  < 0.0001); 25% (22/88) were HBeAg positive with prevalence in countries ranging from 10.5% to 39%. Fifty-two percentage (40/77) of those with HBV received ARV, the majority (97%) received 3TC as the only HBV active agent. HBeAg positivity was associated with high maternal HBV VL, odds ratio (OR) 37.0, 95% confidence interval (CI) 5.4-252.4. Of those with high HBV VL, 40% (4/10) were receiving HBV active drugs (HBV-ARV). HBV drug resistance occurred in 7.5% (3/40) receiving HBV-ARV. CONCLUSIONS: In SSA, HBV co-infection is common in pregnant women with HIV. HBsAg and HBeAg prevalence vary widely by country in this clinical trial cohort. HBeAg is a surrogate for high HBV viral load. HBV drug resistance occurred in 7.5% receiving HBV-ARV with lamivudine as the only HBV active agent. These findings reinforce the importance of HBsAg screening and early treatment with two active agents for HBV.

High Incidence Rate of Computed Tomography-Measured Steatotic Liver Disease in Men With and Without HIV Infection.

INTRODUCTION: We determined steatotic liver disease (SLD) incidence in a prospective cohort of men with HIV (MWH) and men without HIV (MWOH). METHODS: Incident SLD was defined using paired noncontrast computed tomography scans performed during 2010-2013 and repeated during 2015-2017. RESULTS: Of 268 men, 173 MWH and 95 MWOH, 33 had incident SLD (11.1%, incidence rate 2.4 and 2.7/100 person-years for MWH and MWOH, respectively). Overall, higher abdominal visceral adipose tissue was independently associated with increased SLD risk. In MWH, increased visceral adipose tissue, insulin resistance, chronic hepatitis B, and cumulative etravirine use were associated with SLD. DISCUSSION: Metabolic factors, but not HIV, were associated with incident SLD. The high incidence rate suggests that SLD will continue to increase in PWH.

Hepatitis B e Antigen-Negative Single Hepatocyte Analysis Shows Transcriptional Silencing and Slow Decay of Infected Cells With Treatment.

BACKGROUND: Nucleos(t)ide analogues (NUCs) rarely cure chronic hepatitis B (CHB) because they do not eliminate covalently closed circular deoxyribonucleic acid, the stable replication template. In hepatitis B e antigen (HBeAg)-positive CHB during NUCs, HBV-infected cells decline slowly and are transcriptionally silenced. Whether these occur in HBeAg-negative CHB is unknown. METHODS: Using paired liver biopsies separated by 2.7-3.7 years in 4 males with HIV and HBeAg-negative CHB at both biopsies and 1 male with HIV who underwent HBeAg seroconversion between biopsies, we quantified amounts of viral nucleic acids in hundreds of individual hepatocytes. RESULTS: In the 4 persistently HBeAg-negative participants, HBV-infected hepatocytes ranged from 6.2% to 17.7% (biopsy 1) and significantly declined in 3 of 4 by biopsy 2. In the HBeAg seroconverter, the proportion was 97.4% (biopsy 1) and declined to 81.9% at biopsy 2 (P < .05). We extrapolated that HBV eradication with NUCs would take >100 years. At biopsy 1 in the persistently HBeAg-negative participants, 23%-56.8% of infected hepatocytes were transcriptionally inactive-higher than we observed in HBeAg-positive CHB-and significantly declined in 1 of 4 at biopsy 2. CONCLUSIONS: In HBeAg-negative CHB on NUCs, the negligible decline in infected hepatocytes is similar to HBeAg-positive CHB, supporting the need for more potent therapeutics to achieve functional cure.

Pathogen exposure misclassification can bias association signals in GWAS of infectious diseases when using population-based common control subjects.

Genome-wide association studies (GWASs) have been performed to identify host genetic factors for a range of phenotypes, including for infectious diseases. The use of population-based common control subjects from biobanks and extensive consortia is a valuable resource to increase sample sizes in the identification of associated loci with minimal additional expense. Non-differential misclassification of the outcome has been reported when the control subjects are not well characterized, which often attenuates the true effect size. However, for infectious diseases the comparison of affected subjects to population-based common control subjects regardless of pathogen exposure can also result in selection bias. Through simulated comparisons of pathogen-exposed cases and population-based common control subjects, we demonstrate that not accounting for pathogen exposure can result in biased effect estimates and spurious genome-wide significant signals. Further, the observed association can be distorted depending upon strength of the association between a locus and pathogen exposure and the prevalence of pathogen exposure. We also used a real data example from the hepatitis C virus (HCV) genetic consortium comparing HCV spontaneous clearance to persistent infection with both well-characterized control subjects and population-based common control subjects from the UK Biobank. We find biased effect estimates for known HCV clearance-associated loci and potentially spurious HCV clearance associations. These findings suggest that the choice of control subjects is especially important for infectious diseases or outcomes that are conditional upon environmental exposures.

A hepatitis B virus (HBV) sequence variation graph improves sequence alignment and sample-specific consensus sequence construction for genetic analysis of HBV.

Hepatitis B virus (HBV) remains a global public health concern, with over 250 million individuals living with chronic HBV infection (CHB) and no curative therapy currently available. Viral diversity is associated with CHB pathogenesis and immunological control of infection. Improved methods to characterize the viral genome at both the population and intra-host level could aid drug development efforts. Conventionally, HBV sequencing data are aligned to a linear reference genome and only sequences capable of aligning to the reference are captured for analysis. Reference selection has additional consequences, including sample-specific 'consensus' sequence construction. It remains unclear how to select a reference from available sequences and whether a single reference is sufficient for genetic analyses. Using simulated short-read sequencing data generated from full-length publicly available HBV genome sequences and HBV sequencing data from a longitudinally sampled individual with CHB, we investigate alternative graph-based alignment approaches. We demonstrate that using a phylogenetically representative 'genome graph' for alignment, rather than linear reference sequences, avoids issues of reference ambiguity, improves alignment, and facilitates the construction of sample-specific consensus sequences genetically similar to an individual's infection. Graph-based methods can therefore improve efforts to characterize the genetics of viral pathogens, including HBV, and may have broad implications in host pathogen research.

No Association of IFNL4 Genotype With Opportunistic Infections and Cancers Among Men With Human Immunodeficiency Virus 1 Infection.

BACKGROUND: IFNL4 genetic variants that are strongly associated with clearance of hepatitis C virus have been linked to risk of certain opportunistic infections (OIs) and cancers, including Kaposi sarcoma, cytomegalovirus infection, and herpes simplex virus infection. As the interferon (IFN) λ family plays a role in response to viral, bacterial, and fungal infections, IFNL4 genotype might affect risk for a wide range of OIs/cancers. METHODS: We examined associations between genotype for the functional IFNL4 rs368234815 polymorphism and incidence of 16 OIs/cancers among 2310 men with human immunodeficiency virus (2038 white; 272 black) enrolled in the Multicenter AIDS Cohort Study during 1984-1990. Our primary analyses used Cox proportional hazards models adjusted for self-reported racial ancestry to estimate hazard ratios with 95% confidence intervals, comparing participants with the genotypes that generate IFN-λ4 and those with the genotype that abrogates IFN-λ4. We censored follow-up at the introduction of highly effective antiretroviral therapies. RESULTS: We found no statistically significant association between IFNL4 genotype and the incidence of Kaposi sarcoma (hazard ratio, 0.92 [95% confidence interval, .76-1.11]), cytomegalovirus infection (0.94 [.71-1.24]), herpes simplex virus infection (1.37 [.68-2.93]), or any other OI/cancer. We observed consistent results using additive genetic models and after controlling for CD4 cell count through time-dependent adjustment or restriction to participants with a low CD4 cell count. CONCLUSIONS: The absence of associations between IFNL4 genotype and these OIs/cancers provides evidence that this gene does not affect the risk of disease from opportunistic pathogens.

Antiviral supramolecular polymeric hydrogels by self-assembly of tenofovir-bearing peptide amphiphiles.

The development of long-acting antiviral therapeutic delivery systems is crucial to improve the current treatment and prevention of HIV and chronic HBV. We report here on the conjugation of tenofovir (TFV), an FDA approved nucleotide reverse transcriptase inhibitor (NRTI), to rationally designed peptide amphiphiles (PAs), to construct antiviral prodrug hydrogelators (TFV-PAs). The resultant conjugates can self-assemble into one-dimensional nanostructures in aqueous environments and consequently undergo rapid gelation upon injection into 1× PBS solution to create a drug depot. The TFV-PA designs containing two or three valines could attain instantaneous gelation, with one displaying sustained release for more than 28 days in vitro. Our studies suggest that minor changes in peptide design can result in differences in supramolecular morphology and structural stability, which impacted in vitro gelation and release. We envision the use of this system as an important delivery platform for the sustained, linear release of TFV at rates that can be precisely tuned to attain therapeutically relevant TFV plasma concentrations.

Characterizing SARS-CoV-2 Transcription of Subgenomic and Genomic RNAs During Early Human Infection Using Multiplexed Droplet Digital Polymerase Chain Reaction.

BACKGROUND: Control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission requires understanding SARS-CoV-2 replication dynamics. METHODS: We developed a multiplexed droplet digital polymerase chain reaction (ddPCR) assay to quantify SARS-CoV-2 subgenomic RNAs (sgRNAs), which are only produced during active viral replication, and discriminate them from genomic RNAs (gRNAs). We applied the assay to specimens from 144 people with single nasopharyngeal samples and 27 people with >1 sample. Results were compared to quantitative PCR (qPCR) and viral culture. RESULTS: sgRNAs were quantifiable across a range of qPCR cycle threshold (Ct) values and correlated with Ct values. The ratio sgRNA:gRNA was stable across a wide range of Ct values, whereas adjusted amounts of N sgRNA to a human housekeeping gene declined with higher Ct values. Adjusted sgRNA and gRNA amounts were quantifiable in culture-negative samples, although levels were significantly lower than in culture-positive samples. Daily testing of 6 persons revealed that sgRNA is concordant with culture results during the first week of infection but may be discordant with culture later in infection. sgRNA:gRNA is constant during infection despite changes in viral culture. CONCLUSIONS: Ct values from qPCR correlate with active viral replication. More work is needed to understand why some cultures are negative despite presence of sgRNA.

Integrated hepatitis B virus DNA maintains surface antigen production during antiviral treatment.

The focus of hepatitis B functional cure, defined as sustained loss of hepatitis B virus (HBV) surface antigen (HBsAg) and HBV DNA from blood, is on eliminating or silencing the intranuclear template for HBV replication, covalently closed circular DNA (cccDNA). However, HBsAg also derives from HBV DNA integrated into the host genome (iDNA). Little is known about the contribution of iDNA to circulating HBsAg with current therapeutics. We applied a multiplex droplet digital PCR assay to demonstrate that iDNA is responsible for maintaining HBsAg quantities in some individuals. Using paired bulk liver tissue from 16 HIV/HBV-coinfected persons on nucleos(t)ide analog (NUC) therapy, we demonstrate that people with larger HBsAg declines between biopsies derive HBsAg from cccDNA, whereas people with stable HBsAg levels derive predominantly from iDNA. We applied our assay to individual hepatocytes in paired tissues from 3 people and demonstrated that the individual with significant HBsAg decline had a commensurate loss of infected cells with transcriptionally active cccDNA, while individuals without HBsAg decline had stable or increasing numbers of cells producing HBsAg from iDNA. We demonstrate that while NUC therapy may be effective at controlling cccDNA replication and transcription, innovative treatments are required to address iDNA transcription that sustains HBsAg production.

Trans-ancestral fine-mapping of MHC reveals key amino acids associated with spontaneous clearance of hepatitis C in HLA-DQß1.

Spontaneous clearance of acute hepatitis C virus (HCV) infection is associated with single nucleotide polymorphisms (SNPs) on the MHC class II. We fine-mapped the MHC region in European (n = 1,600; 594 HCV clearance/1,006 HCV persistence) and African (n = 1,869; 340 HCV clearance/1,529 HCV persistence) ancestry individuals and evaluated HCV peptide binding affinity of classical alleles. In both populations, HLA-DQß1Leu26 (p valueMeta = 1.24 × 10-14) located in pocket 4 was negatively associated with HCV spontaneous clearance and HLA-DQß1Pro55 (p valueMeta = 8.23 × 10-11) located in the peptide binding region was positively associated, independently of HLA-DQß1Leu26. These two amino acids are not in linkage disequilibrium (r2 < 0.1) and explain the SNPs and classical allele associations represented by rs2647011, rs9274711, HLA-DQB1∗03:01, and HLA-DRB1∗01:01. Additionally, HCV persistence classical alleles tagged by HLA-DQß1Leu26 had fewer HCV binding epitopes and lower predicted binding affinities compared to clearance alleles (geometric mean of combined IC50 nM of persistence versus clearance; 2,321 nM versus 761.7 nM, p value = 1.35 × 10-38). In summary, MHC class II fine-mapping revealed key amino acids in HLA-DQß1 explaining allelic and SNP associations with HCV outcomes. This mechanistic advance in understanding of natural recovery and immunogenetics of HCV might set the stage for much needed enhancement and design of vaccine to promote spontaneous clearance of HCV infection.

Ethical Issues in Genetics and Infectious Diseases Research: An Interdisciplinary Expert Review.

PURPOSE: Research in genetics and infectious diseases (ID) presents novel configurations of ethical, legal, and social issues (ELSIs) related to the intersection of genetics with public health regulations and the control of transmissible diseases. Such research includes work both in pathogen genetics and on the ways that human genetics affect responses to ID. This paper identifies and systematizes the unique issues at this intersection, based on an interdisciplinary expert review. BASIC PROCEDURES: This paper presents results of a formal issue-spotting exercise among twenty experts in public health, law and genomics, biobanking, genetic epidemiology, ID medicine and public health, philosophy, ethics and ID, ethics and genomics, and law and ID. The focus of the exercise was on the collection, storage, and sharing of genetic information relating to ID. MAIN FINDINGS: The issue-spotting exercise highlighted the following ELSIs: risks in reporting to government authorities, return of individual research results, and resource allocation - each taking on specific configurations based on the balance between public health and individual privacy/protection. PRINCIPAL CONCLUSIONS: The public health implications of interactions between genomics and ID frame considerations for equity and justice. In the context of the COVID-19 pandemic, these issues are especially pressing.

Longitudinal Changes in Sex Hormone-Binding Globulin in Men With HIV.

BACKGROUND: Sex hormone-binding globulin (SHBG) is a glycoprotein that regulates sex hormone bioavailability and increases with age in the general population. SHBG concentrations are higher in people with HIV, a population in whom accelerated aging has been hypothesized. It is unclear whether longitudinal changes in SHBG increase over time and differ by HIV serostatus. METHODS: In a longitudinal study, SHBG was measured in 182 men with HIV (MWH) and 267 men without HIV (seronegative) from the Multicenter AIDS Cohort Study and matched for age, race, site, and time, with ≥2 SHBG serum samples over the 10 years after HAART initiation. Multivariable linear mixed-effects regression models were used to evaluate whether log-transformed SHBG [ln(SHBG)] and its rate of change differed by HIV serostatus. RESULTS: At baseline, the mean age in MWH was similar to that in HIV-seronegative men (51 ± 5 vs 49 ± 6 years). However, SHBG mean values were higher in MWH compared with those in HIV-seronegative men (65.6 ± 48.8 vs. 45.4 ± 22 nmol/L, P < 0.001). In a fully adjusted model, SHBG increased over time and at a faster rate in MWH compared with that in HIV-seronegative men: [2.0%/year (95% CI: 1.4 to 2.7) vs 1.3%/year (95% CI: 0.8 to 1.8), respectively, P = 0.038]. Among MWH, higher SHBG concentrations were significantly associated with lower CD4+ T-cell count [ß= -0.02 (95% CI: -0.03 to -0.0002), P < 0.05], fewer cumulative years on zidovudine [ß = -0.027 (95% CI: -0.045 to -0.009), P < 0.001], and greater cumulative years on nonnucleoside reverse transcriptase inhibitors drugs [ß = 0.022 (95% CI: 0.0006 to 0.04), P < 0.05]. CONCLUSIONS: Aging-related increases in SHBG were faster in MWH compared with those in HIV-seronegative men and were related to poorer immunologic status and antiretroviral medication exposure. The mechanisms and consequences of these findings require further investigation.

Outcomes of acute hepatitis B virus (HBV) in HIV infection with and without HBV-active antiretroviral therapy.

Men with acute hepatitis B virus (HBV) infection in the Multicenter AIDS Cohort Study from 1985 to 2013 had serological testing to determine proportions with HBV recovery or chronic hepatitis B (CHB). A similar proportion of men without human immunodeficiency virus (HIV) and men with HIV receiving HBV-active antiretroviral therapy (ART) developed CHB [8.2%, 95% confidence interval (CI) 3.8-15.0% vs. 7.7%, 95% CI 2.00-36.0%]. In contrast, 17.5% (95% CI 8.7-29.9%) of men living with HIV, not on HBV-active ART developed CHB. HBV-active ART protects against developing CHB.

HBV co-infection is associated with persistently elevated liver stiffness measurement in HIV-positive adults: A 6-year single-centre cohort study in Nigeria.

BACKGROUND: In Nigeria, the effect of Hepatitis B virus (HBV) on long-term liver outcomes in persons with HIV (PLH) has not been described. We determined changes in liver stiffness measure (LSM) using transient elastography over 6 years in HIV mono-infected and HIV-HBV co-infected Nigerians initiating antiretroviral therapy (ART) and factors associated with LSM decline. METHODS: This single centre, cohort study enrolled ART-naïve HIV mono- and HIV-HBV co-infected adults (≥18 years) at the APIN Public Health Initiatives-supported HIV Care and Treatment Centre at Jos University Teaching Hospital, Nigeria, from 7/2011 to 2/2012. LSM at baseline, Years 3 and 6 were analysed using longitudinal models to estimate changes over time and their predictors. RESULTS: Data from 100 (31%) HIV-HBV co-infected and 225 (69%) HIV mono-infected participants were analysed. Median LSM at baseline was 6.10 (IQR: 4.60-7.90) kPa in co-infected and 5.10 (IQR: 4.40-6.10) kPa in mono-infected participants. In adjusted analyses, average LSM was not significantly different between Year 0 and 3 (ß = 0.02, -0.22 to 0.26, p = 0.87 and Year 0 and 6 (ß = -0.02, -0.23 to 0.27, p = 0.88) in both groups (p>0.05), but co-infected participants had significantly higher LSM than mono-infected throughout follow-up (ß = 0.018, 0.019-0.28, p < 0.001). Year 3 LSM differed according to ART initiation status by Year 3 (initiators - non-initiators: -0.87, -1.70 to -0.29). CONCLUSION: In this cohort, LSM remained higher among HIV-HBV co-infected versus HIV mono-infected participants throughout follow-up. Our findings emphasize the continuing need for monitoring of liver outcomes in HIV-HBV co-infected populations on ART and the importance of preventing HBV infection among PLH to optimize liver health.

A Multiancestry Sex-Stratified Genome-Wide Association Study of Spontaneous Clearance of Hepatitis C Virus.

BACKGROUND: Spontaneous clearance of acute hepatitis C virus (HCV) infection is more common in women than in men, independent of known risk factors. METHODS: To identify sex-specific genetic loci, we studied 4423 HCV-infected individuals (2903 male, 1520 female) of European, African, and Hispanic ancestry. We performed autosomal, and X chromosome sex-stratified and combined association analyses in each ancestry group. RESULTS: A male-specific region near the adenosine diphosphate-ribosylation factor-like 5B (ARL5B) gene was identified. Individuals with the C allele of rs76398191 were about 30% more likely to have chronic HCV infection than individuals with the T allele (OR, 0.69; P = 1.98 × 10-07), and this was not seen in females. The ARL5B gene encodes an interferon-stimulated gene that inhibits immune response to double-stranded RNA viruses. We also identified suggestive associations near septin 6 and ribosomal protein L39 genes on the X chromosome. In box sexes, allele G of rs12852885 was associated with a 40% increase in HCV clearance compared with the A allele (OR, 1.4; P = 2.46 × 10-06). Septin 6 facilitates HCV replication via interaction with the HCV NS5b protein, and ribosomal protein L39 acts as an HCV core interactor. CONCLUSIONS: These novel gene associations support differential mechanisms of HCV clearance between the sexes and provide biological targets for treatment or vaccine development.

HIV Prevention Trials Network 078: High Prevalence of Hepatitis C Virus Antibodies Among Urban US Men Who Have Sex With Men, Independent of Human Immunodeficiency Virus Status.

BACKGROUND: Sexual transmission of hepatitis C virus (HCV) is uncommon, yet documented among men who have sex with men (MSM), primarily among those with human immunodeficiency virus (HIV). METHODS: In the HIV Prevention Trials Network 078 study (HPTN 078), which assessed an integrated strategy to achieve HIV viral suppression, 1305 MSM were screened across 4 geographically diverse US cities. At screening, demographic/behavioral/psychosocial questionnaires were completed, along with HIV and HCV testing. Multivariable logistic regression was used to evaluate associations with HCV antibody positivity. RESULTS: Among the 1287 (99%) of the MSM with HCV antibody results, the median age was 41, 69% were black, 85% had a high school education or more, 35% were employed, 70% had HIV, and 21% had undergone substance use counseling. The median lifetime number of male sexual partners was 17 (interquartile range, 6-50), and 246 (19%) were HCV antibody positive. HCV antibody positivity was high in MSM with HIV (20%) and MSM without HIV (17%) (P = .12) and was higher in those receiving substance use counseling (36%) than in those who had not (15%) (P ≤ .01). Substance use counseling (odds ratio, 2.51; 95% confidence interval, 1.80-3.51) and unstable housing (2.16; 1.40-3.33) were associated with HCV antibody positivity. CONCLUSIONS: Nearly 1 in 5 MSM screened for HPTN 078 have been infected with HCV. The prevalence is high regardless of HIV status and is high even in those who did not undergo substance use counseling. In HIV burden networks, high HCV infection prevalence may occur in MSM without HIV. As implementation of preexposure prophylaxis expands and condom use declines, routine HCV counseling and screening among MSM are important.

Maternal HBV Viremia and Association With Adverse Infant Outcomes in Women Living With HIV and HBV.

BACKGROUND: There is limited information on perinatal outcomes in HIV-hepatitis B virus (HBV) coinfection. METHODS: HIV Prevention Trials Network (HPTN) 046 was a randomized double-blind placebo-controlled trial of perinatal transmission that evaluated 6 months of infant nevirapine versus placebo among breast-fed infants. Women living with HIV and their infants enrolled in sub-Saharan Africa from 2007 to 2010; 78% received antiretroviral therapy (ART). Maternal samples were tested for hepatitis B surface antigen (HBsAg). High and low HBV viral load (VL) was defined as ≥106 IU/mL and <106 IU/mL. The association between HIV-HBV coinfection and maternal and infant outcomes was assessed using multivariate (MV) logistic and Cox regression. RESULTS: Among 2025 women, 88 (4.3%) had HBV. HIV-HBV women with high HBV VL had lower median CD4, versus HIV alone or HIV-HBV women with low HBV VL [320, 490 and 434 cells/mm3, respectively (P < 0.007)]. In MV analysis, adjusted for maternal CD4, age and maternal ART, infants born to women with high HBV VL were more likely to be low birth weight (LBW), versus HIV+/HBV- and low HBV VL women: [30% (3/10) vs. 10% (194/1953) vs. 6% (5/78), respectively, P = 0.03). High HBV VL was associated with HIV perinatal transmission [(hazard ratio 6.75 (95% confidence interval (CI): 1.86 - 24.50)]. There was no impact on infant mortality or maternal outcomes at 18 months. CONCLUSIONS: In HIV-HBV women, high HBV viral loads increase the risk of LBW and potentially HIV perinatal transmission. Reduction of antepartum HBV viremia may have beneficial effects beyond the prevention of HBV perinatal transmission.

Direct-Acting Antiviral Hepatitis C Treatment Cascade and Barriers to Treatment Initiation Among US Men and Women With and Without HIV.

BACKGROUND: People with HIV are disproportionately coinfected with hepatitis C virus (HCV) and experience accelerated liver-related mortality. Direct-acting antivirals (DAAs) yield high sustained virologic response (SVR) rates, but uptake is suboptimal. This study characterizes the DAA-era HCV treatment cascade and barriers among US men and women with or at risk for HIV. METHODS: We constructed HCV treatment cascades using the Women's Interagency HIV Study (women, 6 visits, 2015-2018, n = 2447) and Multicenter AIDS Cohort Study (men, 1 visit, 2015-2018, n = 2221). Cascades included treatment-eligible individuals (ie, HCV RNA-positive or reported DAAs). Surveys captured self-reported clinical (eg, CD4), patient (eg, missed visits), system (eg, appointment access), and financial/insurance barriers. RESULTS: Of 323/92 (women/men) treatment eligible, most had HIV (77%/70%); 69%/63% were black. HIV-positive women were more likely to attain cascade outcomes than HIV-negative women (39% vs 23% initiated, 21% vs 12% SVR); similar discrepancies were noted for men. Black men and substance users were treated less often. Women initiating treatment (vs not) reported fewer patient barriers (14%/33%). Among men not treated, clinical barriers were prevalent (53%). CONCLUSIONS: HIV care may facilitate HCV treatment linkage and barrier navigation. HIV-negative individuals, black men, and substance users may need additional support. CLINICAL TRIALS REGISTRATION: NCT00000797 (Women's Interagency HIV Study); NCT00046280 (Multicenter AIDS Cohort Study).

Genomics in the era of COVID-19: ethical implications for clinical practice and public health.

Genomic studies of patients with COVID-19, or exposed to it, are underway to delineate host factors associated with variability in susceptibility, infectivity, and disease severity. Here, we highlight the ethical implications-both potential benefits and harms-of genomics for clinical practice and public health in the era of COVID-19.